Cannabis and Mental Illness ( Psychosis/schizophrenia )

By Mary Brett

In the last few years increasing concern has been expressed about the association of cannabis with mental illness. The number of cannabis users is going up. In the USA in some age groups, almost as many people are smoking cannabis as cigarettes. Children are starting to use the drug at an increasingly early age, more and more studies are emerging which link cannabis use with psychological and social problems, demand for treatment for cannabis users is rising and there is a change in the THC content of some cannabis varieties. Selectively bred strains such as skunk and nederweed have much greater percentages of THC than did the marijuana of the sixties and seventies.

Jan Ramstrom, the Swedish psychiatrist and expert on substance abuse who wrote Adverse Health Consequences of Cannabis Use (2003) said, “ At present we find ourselves in a curious situation where researchers and clinicians are becoming even more concerned, while the general public, not least in Europe, seems to grow less concerned”.

He also said, “It is worth mentioning that the opiates (heroin etc), apart only from the development of dependence, produce far fewer toxic psychiatric complications than do cannabis preparations”

Two fundamentally different psychotic manifestations are involved.

Toxic psychosis:
Cannabis-induced psychotic disorder, recognised as a diagnostic unit in the DSM 1V (Diagnostic and Statistical Manual of Mental Disorders) is caused by the toxic effects of the drug and involves a group of brain damage syndromes. The symptoms are caused by cannabis consumption and subside when drug use ceases. The use of anti-psychotic medicines to eliminate any residual symptoms means most patients make a full recovery unless he or she resumes the taking of cannabis or indeed other drugs. Symptoms of delirium often dominate, i.e. bewilderment and memory disturbance. Paranoia, hallucinations and aggression alternating with euphoria also occur. There is usually an absence of any heredity factor.

Functional psychosis:
“Functional” in this sense applies to the absence of organic damage. Cullberg 2000, said that there probably is some organic damage, possibly taking the form of some subtle vulnerability as yet unknown. This category covers schizophrenia and schizophrenia-like psychosis which usually runs a chronic course. Symptoms of delirium are absent and there is often a feeling of outside interference with thought. Often the person has a “premorbid personality” with extreme reserve, loss of interest and bizarre suspicious ideas.

To quote Jan Ramstrom again, “…what we are dealing with here are the most profound disturbances known to psychiatry; even when they are short-lived, such disturbances can leave marks on those affected and on their families which may remain for many years or even be of life-long duration.…..there is both an abuse condition and a serious mental disorder. These “dual disorders” are among the most difficult to assess in the whole of psychiatry. Moreover, conditions of this type not rarely make demands on the most costly resources available in the field of psychiatric care”.

Early Studies.
Papers as early as the 1970s saw researchers connecting cannabis consumption with psychosis.

1972. Tennant and Groesbeck studied American soldiers in Europe and found large numbers abusing drugs mostly hashish. Between 1968 and 1971, the number of acute psychotic reactions, not necessarily leading to schizophrenia increased from 16 in 1968 to 77 in 1971, an almost 5-fold increase in 4 years. They concluded that hashish smoking was the major contributor.

1974. Chopra and Smith described 200 patients admitted to a Calcutta psychiatric hospital between 1963 and 1968 with psychotic symptoms following cannabis use. Most cases were preceded by the ingestion of large quantities. One third had no previous psychiatric history and the symptoms were the same regardless of their history. The most potent cannabis preparations resulted in psychotic reactions in the shortest period of time.

1974. DA Treffert allowed 4 schizophrenic patients, all on anti-psychotic medicine to act as their own controls. Having been warned not to, all of them smoked cannabis occasionally. All of them experienced deterioration in their condition, sometimes with very serious consequences. This clearly demonstrated that there was a direct association between relapses into pot smoking and serious deterioration in the schizophrenia condition.

1974. Breakey and others pointed to some sort of association between drug use, including cannabis, and the onset of schizophrenic illness. He considered that cannabis and other drugs could precipitate latent schizophrenia, but also thought that cannabis could do this in cases where the illness would not occur otherwise. They based this conclusion on the fact that the drug induces schizophrenia on average 4 years earlier than the onset in other types of schizophrenia. The onset was also more sudden, and the premorbid personality always better than a comparative group of non-drug using schizophrenics.

1976. Thacore and Shukla made a clear attempt to demonstrate the occurrence of a specific cannabis-provoked functional psychosis.

Other papers around this time, giving support to the findings include, Talbott and Teague 1969, Weil 1970, Bernardson and Gunne 1972 and Harding and Knight 1973.

So even as long ago as the early seventies some researchers were trying to ring alarm bells about the possible psychological problems of cannabis use.

The eighties brought another crop of papers on the subject.

1981. MB Holmberg found that 10% of 16 year-old consumers of large quantities of drugs, almost exclusively cannabis, by the age of 27, would have a record of psychosis. This was much higher than the 3% in the normal population.

1985. Bier and Haastrup looked at psychological admissions over one year in a Copenhagen hospital. Thirty patients had cannabis-provoked psychosis. They then estimated that 15 in a population of 100,000 would be admitted each year with psychosis either precipitated or caused by cannabis.

1986. Negrette and others concluded that interaction between cannabis smoking and schizophrenia had the following characteristics. Cannabis smokers have more relapses, more hospital visits, the positive symptoms of schizophrenia are more dramatic and the patients are less susceptible to neuroleptic medication.

1986. Ghodse said there was clear evidence from countries where heavy cannabis use is common, that cannabis causes a short-term toxic psychosis. This was supported by laboratory experiments.

Among the large body of reports from researchers and clinicians at this time are the following: Palsson, Thulin and Tunving 1982, Rottamburg et al 1982, Tsuang et al 1982, Carney 1984, Brook 1984, Tunving 1985 and Hollister 1986.

However the most important publication at this time was the large study of Swedish conscripts by Andreasson, Allebeck et al in 1987.

Forty-five thousand conscripts had their drug-taking details taken at entry, aged 18 or 19. The levels of schizophrenia were then recorded over the next 15 years. Those on admission who claim to have taken cannabis on more than 50 occasions were found to be 6 times more likely to be diagnosed with schizophrenia in the following 15 years than those who had never consumed the drug. When confounding factors were taken into account, the risk became smaller but remained statistically significant.

Although the study attracted some criticisms, Negrette, the doyen in this field judged the connection to be reasonable taking other previous studies into account, while accepting there were some weaknesses. Andreasson in 1989 and Allebeck in 1993 strengthened their position by further research. They examined the medical records of 112 cannabis-dependent and schizophrenic patients. The findings in all significant respects confirmed the original study.

Further support came from the analysis of records of 100 schizophrenic patients between 1973 and 1977 randomly chosen by Dalman et al in 2002. A large measure of consistency was established with respect to regions, hospitals and timescale as well as the diagnostic criteria for schizophrenia, DSM-1V.

Over twenty years later in 2002, Zammit and others re-analysed the results. In the light of new research into the development of schizophrenia, they were able to discount more of the original objections.

Research continued in the nineties.

1990. Tien and Anthony conducted an epidemiological analysis of drug and alcohol use and concluded that there was an association between cannabis use and psychosis. Daily use over a year suggested a 2.4 times greater risk than non-users, any use related to a risk of 1.3 times. The daily risk figure remained significant after adjustment for other substance abuse and baseline psychiatric diagnosis.

1991. Johnson, from his own long experience and a review of the current literature, estimated that 10% of all of those who had used cannabis more than once, experienced either delirium or psychosis. Later estimates confirmed this figure, notably Thomas in 1996 who sent questionnaires to young new Zealanders. Johns as recently as 2001 supported this claim.

1995. Wylie observed a group of British consumers of Dutch cannabis with a high THC content. He recorded a “wave of psychosis and confusional states”. The risk therefore becomes greater the more often cannabis is used and the greater its strength.

1998. Hall concluded that cannabis can cause psychotic like symptoms during intoxication, can lead to a “cannabis psychosis” to increase the relative risk of schizophrenia, and affect the clinical course of established schizophrenia.

A paper by J Giedd et al in 1999 on development of the adolescent brain must be mentioned here. They conclude that the brain does not finish its development till the mid twenties or beyond. So the warning is that drug abuse could alter the normal course of the maturing of the brain in the teenage years. Research by Giedd on this subject is on-going.

Since the year 2000 there has been a flood of publications. 2002. Louise Arsenault et al assessed 1100 New Zealand children at 11, 15, 18 and 26. Young adults smoking cannabis at the age of 15 were at a greater risk of developing schizophrenia or a schizophrenia-like illness by the age of 26. The risk was 10% times compared to 3% for non-users. Use at 15 was a stronger risk factor for schizophreniform disorder than use by the age of 18.

2002. The Nemesis Study by Van Os et al studied 4045 psychosis-free Dutch people and 59 who had a psychotic disorder, taken at random from 60 localities. They concluded that it must be considered proven that smoking cannabis can provoke a functional (non-toxic) schizophrenia-like psychosis. They replicated the Swedish study of Andreasson. It was of shorter duration and had fewer participants, but not the weaknesses. There was a baseline assessment and 2 follow up sessions, after 1 and 3 years, by questionnaire and clinical interviews. The study showed that individuals using cannabis at baseline were almost 3 times more likely to manifest psychotic symptoms at follow up. After confounding factors were taken into account the risk remained significant. A dose-response relationship was also found. The risk factor for the heaviest users rose to 6.8. They concluded: “cannabis use is an independent risk factor for the emergence of psychosis in psychosis-free persons and that those with an established vulnerability to psychotic disorders are particularly sensitive to its effects, resulting in poor outcome”.

2002. Nunez and Gurpegui compared 26 patients with cannabis-induced psychosis to 35 with acute schizophrenia. All used cannabis, they were repeatedly urine tested. They concluded that cannabis when continuously and heavily used can induce a psychotic disorder distinct from acute schizophrenia.

2002. Hiroshi Ujike found genetic abnormalities in the genes for the cannabinoid receptors on the brain cells of schizophrenics compared to non-schizophrenics. This implies a potential malfunction of their marijuana-linked circuitry, perhaps making them more vulnerable to schizophrenia.

Many people have argued and it seems logical that if the use of cannabis has increased then so must the incidence of schizophrenia.

2003. Boydell et al found that there was indeed a continuous and statistically significant rise in the incidence of schizophrenia between 1965 and 1997. It had doubled over the last 3 decades. The increase was greatest in people under 35.

2003. The Christchurch Health and Development Study. Fergusson et al looked at 1200 children from birth to the age of 21. The cannabis-dependent youngsters developed psychotic symptoms more often than those who were non-dependent. Individuals with cannabis-dependence disorder at 18 had a 3.7-fold increased risk of psychosis than those with no dependence disorder. At 21 the risk fell to 2.3 times.

They conclude that: “the findings are clearly consistent with the view that heavy cannabis use may make a causal contribution to the development of psychotic symptoms since they show that, independently of pre-existing psychotic symptoms and a wide range of social and contextual factors, young people who develop cannabis dependence show an elevated rate of psychotic symptoms”.

They found that adolescent neurodevelopment occurs in brain regions associated with motivation, impulsivity and addiction. These developmental processes may advantageously promote learning drives for adaptation to adult roles but may also confer greater vulnerability to the addictive actions of drugs. This has significant implications for understanding adolescent behaviour, addiction vulnerability and the prevention of addiction in adolescence and adulthood.

2004. Veen et al. One hundred and thirty-three Dutch patients with schizophrenia were interviewed. There was a strong association between the use of cannabis and an earlier age of first psychotic episode in male schizophrenics. On average they were 6.9 years younger than non-using patients.

2004. D’Souza et al. Various doses of THC were administered to 22 healthy subjects, screened for any vulnerability to schizophrenia. Some of them developed symptoms resembling schizophrenia for 30 minutes to 1 hour. There were no side effects after 1, 3 and 6 months. The study findings go along with several other lines of evidence that suggest a contribution of cannabis and/or abnormalities in the brain cannabinoid receptor system to the pathophysiology of schizophrenia.

Conclusion: Co-morbid psychiatric disorders are common among heavy cannabis users seeking treatment. Some psychiatric disorders occur more frequently in this group compared to users of other substances.

2005. Isaac and Holloway did their research in PICUs (Psychiatric Intensive Care Units). There was a high rate of cannabis abuse (71.3%) among the PICU population. Patients with cannabis abuse spent longer as their psychosis was more severe. They were also younger at first hospital admission. The conclusion was that cannabis abusers have more severe psychotic illness especially in schizophrenia. There are additional problems of weight gain.

2004. Frischer et al from Keele University monitored 3% of the population of England and Wales. The number of people using drugs and having mental illness rose by 62% between 1993 and 1998. (230 GP practices were looked at). Men accounted for 79% and women 44%.

The average age affected fell from 38 to 34. The number of cases of 25 to 34 year olds more than doubled. Drug abuse and psychosis were up by 147%, paranoia by 144% and schizophrenia by 128%.

They said, “A long-term, well funded, innovative campaign aimed at publicising the real mental health risks associated with drugs including cannabis needs to be in place as soon as possible”.

2004. Stephanis et al looked at 3500 19-year olds in Greece. Conclusions: These results add credence to the hypothesis that cannabis contributes to the population level of expression of psychosis. In particular, exposure early in adolescence may increase the risk for the sub-clinical positive and negative dimensions of psychosis, but not for depression.

2005. Favrat et al. Clinical trials of THC on psychomotor function and driving performance were conducted on 8 occasional cannabis users with no history of psychosis. Low doses were used. Two young men reacted badly. One 22 year-old showed severe anxiety and psychotic symptoms 90 minutes later, and was unable to do the tests. The other, also 22, was unable to do the tests for several hours, and experienced very unpleasant symptoms.

The doses were administered under clinical conditions and were much lower than would normally be found in a modern joint. The importance of this research is that oral administration of the THC caused significant psychotic reactions. Oral medicines are becoming increasingly available and doctors should be aware of these findings.

2005. Ferdinand. The “Zuid Holland” Study, a 14 year follow up study of 1580, initially 4 to16 year olds, drawn randomly from the Dutch population. (Because cannabis use is generally condoned in Holland, false negative reports of cannabis use may occur less frequently. This adds to the value of this study). Findings: Cannabis use in individuals who did not have psychotic symptoms before they began using cannabis, predicted future psychotic symptoms, the risk was almost 3 times greater. Also psychotic symptoms in those who had never used cannabis before the onset of psychotic symptoms also predicted future cannabis use.

Conclusion: The results either imply a common vulnerability with varying order of onset or a bi-directional causal relationship between cannabis use and psychosis.

2005. Van Os et al. Nearly 2500 young people between the ages of 14 and 24, with or without predisposition to psychosis were studied. Adjustment was done for confounding factors such as alcohol, cigarettes and other drugs. There was a dose-response relationship with increasingly frequent use of cannabis.

Conclusions: Cannabis use in young people moderately increased the risk of developing psychotic symptoms. The risk for onset of symptoms was much higher in young people with a predisposition for psychosis. Predisposition psychosis at baseline did not predict cannabis use at follow up. This rejects the self-medication hypothesis i.e. that psychotic patients take drugs to relieve the symptoms of the illness.

2005. Fergusson et al. This was a 25 year longitudinal study of 1055 New Zealand children from birth. Conclusions: “Even when all factors were taken into account, there was a clear increase in rates of psychotic symptoms after the start of regular use, with daily users of cannabis having rates that were over150% those of non-users. These findings add to a growing body of evidence from different sources, all of which suggest that heavy use of cannabis may lead to increased risks of psychotic symptoms and illness in susceptible individuals”.

Several review articles have also appeared in the last few years.

2001. Johns. Conclusion: “Heavy cannabis misuse leads to the risk of psychotic episodes and aggravates the symptoms and course of schizophrenia. For any psychiatric patient, risk management and care planning is incomplete without a thorough assessment of substance abuse”. 2003. Degenhardt and Hall. Conclusion: “Cannabis use does not appear to be causally related to the incidence of schizophrenia but its use may precipitate disorders in persons who are vulnerable to develop psychosis and worsen the course of the disorder among those who have already developed it”.

2004. Arsenault et al. A review of 5 papers was undertaken: The Swedish Conscript cohort, Andreasson 1987 and Zammit et al 2002. The Dutch Nemesis Sample, Van Os 2002. The Christchurch Study, Fergusson et al 2003. The Dunedin Study, Arsenault 2002. The overall conclusion: “A twofold increase in the relative risk for later schizophrenia. At the population level, elimination of cannabis smoking would reduce the incidence of schizophrenia by around 8% assuming a causal relationship. Cannabis is a component cause for psychosis, part of a complex constellation of factors”.

2004. Rey et al. Conclusion: The weight of evidence points in the direction of early and regular use of cannabis having substantial negative effects on psychosocial functioning and psychopathology.

2004. Drewe et al. This article appeared in response to the potential legalization of cannabis in Switzerland. Conclusion: “An increase in consumption would be expected therefore there would probably be an increase in the prevalence of psychosis, not only acute toxic but also chronic psychosis. Schizophrenic psychoses would be expected to be triggered at an earlier age so there could be deleterious consequences not only for many currently healthy individuals but for disablement pensions”.

2004. Raphael and Wooding. Conclusion: “Of primary importance is the fact that cannabis use does have a number of significant associated harms. It is not a soft or safe option and its notable co-morbidity with psychotic and non-psychotic illnesses make it a significant and growing public health issue – a fact increasingly reflected in both the national and international scientific literature”.

Professor Robin Murray of the Institute of Psychiatry, London, drew attention to the fact in 2003 that recent evidence had demonstrated that THC increases the release of dopamine, thus increasing its level in the brain. Psychotic symptoms in conditions like schizophrenia are mediated by dopamine.

Two important papers are awaiting publication in scientific journals.

Caspi et al. in a paper to be published in Biological Psychiatry, have found variants in a gene (COMT) which is involved in dopamine transmission. It was found to moderate the influence of adolescent cannabis use on the development of adult psychosis. One in four people carries this gene. The research was carried out on 803 men and women born in Dunedin, New Zealand in 1972 and 1973. They were enrolled at birth. The gene comes in 2 variants, methionine and valine, and everyone has two copies of the gene. If a person inherits 2 methionine types, the rate of psychotic illness is 3%, the normal rate for non-users. However if a person has 2 valine variants, the rate rises to 15% for those who have used cannabis in their teens. Dr Caspi said, “Research has shown that the valine gene variant and cannabis affect the brain’s dopamine system in similar fashion, suggesting that they deliver a “double dose” that can be damaging”.

Markus Leweke and others from the University of Cologne in Germany addressed The International Cannabis and Mental Health Conference in Melbourne in August 2004.

The brain’s “natural cannabis” is a substance called anandamide. Much higher levels of this chemical were found in the brains of schizophrenics experiencing their first psychotic episode and before they had embarked on medication for their condition, and also the brains of people with psychotic symptoms and a strong susceptibility to schizophrenia.

Surprisingly the more severe the schizophrenia, the lower the levels of anandamide. They postulated that anandamide may actually be produced to control psychotic symptoms and dampen them down. THC binds to anandamide receptors. It makes these receptor sites less sensitive and may disrupt the system in other ways as well.

An article appeared in New Scientist in August 2004.

In 2004 Marijuana and Madness was published by Cambridge University Press. The editors were, Professor David Castle of The Mental Health Research Unit, Melbourne, and Professor Robin Murray of The Institute of Psychiatry in London.

Twenty-nine contributors to 13 chapters are listed. Many of them have been mentioned in this article. The review from the journal “Addiction” says:

“Each chapter is well written and well presented…There is little doubt that the chapters are expertly written…Marijuana and madness illustrates clearly the benefits of a multi-disciplinary perspective in providing the tools for answering a complex question”.

Mary Brett, retired biology teacher and former Head of Health Education Dr Challoner’s Grammar School Amersham Bucks. May 9th 2005.